调节因子 X1 通过促进自身免疫炎症中的 DNA 去甲基化诱导巨噬细胞 M1 极化。
Regulatory factor X1 induces macrophage M1 polarization by promoting DNA demethylation in autoimmune inflammation.
机构信息
Department of Dermatology, Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Medical Epigenomics, Changsha, China.
Research Unit of Key Technologies of Diagnosis and Treatment for Immune-related Skin Diseases, Chinese Academy of Medical Sciences, Central South University, Changsha, China.
出版信息
JCI Insight. 2023 Oct 23;8(20):e165546. doi: 10.1172/jci.insight.165546.
Abnormal macrophage polarization is generally present in autoimmune diseases. Overwhelming M1 macrophage activation promotes the continuous progression of inflammation, which is one of the reasons for the development of autoimmune diseases. However, the underlying mechanism is still unclear. Here we explore the function of Regulatory factor X1 (RFX1) in macrophage polarization by constructing colitis and lupus-like mouse models. Both in vivo and in vitro experiments confirmed that RFX1 can promote M1 and inhibit M2 macrophage polarization. Furthermore, we found that RFX1 promoted DNA demethylation of macrophage polarization-related genes by increasing APOBEC3A/Apobec3 expression. We identified a potential RFX1 inhibitor, adenosine diphosphate (ADP), providing a potential strategy for treating autoimmune diseases.
异常的巨噬细胞极化通常存在于自身免疫性疾病中。过度的 M1 巨噬细胞激活促进了炎症的持续进展，这是自身免疫性疾病发展的原因之一。然而，其潜在机制尚不清楚。在这里，我们通过构建结肠炎和狼疮样小鼠模型来探索调节因子 X1（RFX1）在巨噬细胞极化中的作用。体内和体外实验均证实，RFX1 可促进 M1 型巨噬细胞极化，抑制 M2 型巨噬细胞极化。此外，我们发现 RFX1 通过增加 APOBEC3A/Apobec3 的表达来促进巨噬细胞极化相关基因的 DNA 去甲基化。我们鉴定出一种潜在的 RFX1 抑制剂——二磷酸腺苷（ADP），为治疗自身免疫性疾病提供了一种潜在的策略。
Zotero 插件